New $16 million center to push, pinch and probe cancer cells & tissues

By Robert Sanders, Media Relations| 26 October 2009

BERKELEY — The National Cancer Institute (NCI) has awarded the University of California, Berkeley, $15.7 million over five years to allow physical scientists and engineers to open a new front in the war on cancer.

UC Berkeley's Physical Sciences-Oncology Center, a collaboration with UC San Francisco (UCSF), Lawrence Berkeley National Laboratory (LBNL) and San Francisco's Helen Diller Comprehensive Cancer Center, is one of 12 centers announced today (Monday, Oct. 26) by the NCI "to bring new perspectives to the mechanisms of cancer," according to the institute's Web site.

"In our center, scientists from across the physical sciences, including chemists, engineers, physicists and mathematicians, will work side-by-side with experienced biologists and oncologists," said biophysicist Jan Liphardt, UC Berkeley associate professor of physics and principal investigator of the center. "Together, these teams will apply the tools and insights of the physical sciences to oncology."

Overall, the network of physical sciences-oncology centers will receive $22.7 million from the NCI in fiscal year 2009, and will focus on physical laws and principles of cancer; evolution and evolutionary theory of cancer; information coding, decoding, transfer and translation in cancer; and ways to de-convolute cancer's complexity.

"By bringing a fresh set of eyes to the study of cancer, these new centers have great potential to advance, and sometimes challenge, accepted theories about cancer and its supportive microenvironment," said NCI Director John E. Niederhuber, M.D. "Physical scientists think in terms of time, space, pressure, heat, and evolution in ways that we hope will lead to new understandings of the multitude of forces that govern cancer - and with that understanding, we hope to develop new and innovative methods of arresting tumor growth and metastasis."

To date, cancer research has primarily focused on mutations in the genome that result in cancer and the signaling molecules and networks involved in cancer initiation, progression and metastasis, Liphardt said. Despite much new information and new drugs such as Herceptin resulting from this research, however, "there is an increasing sense that there are additional promising directions that need to be explored."

One of those frontiers is mechanobiology, which seeks to understand how mechanical forces affect proteins, cells and tissues. Mechanical forces change how proteins cluster in membranes, affecting signaling, and also provide specific guidance to cells and tissues that tell them where to divide and how to arrange themselves.

Liphardt's lab, for example, uses super-resolution microscopy to count and follow the movement of individual proteins in a cell's outer membrane or in its nucleus. His lab also uses optical and magnetic tweezers to grab single molecules and watch them bend and unfold.

"Physical scientists have long relied on precision measurement and manipulation of dynamical systems to figure out how they work, and one of the things we are going to do is make sure that all these tools and methods are available to the oncology community," Liphardt said.

At UCSF, senior co-investigator Valerie Weaver, an associate professor of surgery and director of the Center for Bioengineering and Tissue Regeneration, will explore how the mechanical characteristics of the extracellular matrix and other aspects of a cancer cell's microenvironment affect its growth, survival and migration. She recently found, for example, that a stiffer extracellular matrix, a web within which cells nestle, promotes breast malignancy in a mouse model.

Other center investigators include Joe W. Gray, a pioneer in characterizing the genomic, transcriptional and proteomic abnormalities that occur in selected cancers. He will be working with Frank McCormick, the director of the Helen Diller Comprehensive Cancer Center, and Jay Groves of UC Berkeley, LBNL and the Howard Hughes Medical Institute, to investigate cell signaling in cancer. Another investigator, LBNL's Mina Bissell, pioneered the idea that a breast cell's microenvironment dramatically influences whether it becomes a cancer cell. She has shown that changing the microenvironment, both chemically and mechanically, can make a mass of malignant cells revert to a less malignant cell aggregate.

Other center scientists, such as UC Berkeley and LBNL mathematician James Sethian and UC Berkeley engineer Claire Tomlin, hope to model the dynamics of cancer cell growth and development and come up with simpler rules that will help researchers understand how these systems work.

"Finding simple and elegant rules will certainly be very hard or may even be impossible, but it is essential to try," Liphardt said. "Physical scientists have had some success taking apparently very, very complex systems and nonetheless identifying some general rules."

In concert with the research, the center will also focus on training and mentoring the next generation of scientists able to work at the interface of oncology and the physical sciences. By developing new classes, hosting seminars and conferences and training graduate students and post-doctoral fellows, Liphardt said he and his colleagues hope to "nucleate a large, multidisciplinary community of physical scientists to help tackle the many open questions in oncology."

"In the long term, of course, the value of the entire initiative will be judged by how much it improves cancer treatment options and outcomes," Liphardt said. "There are already new ideas. For example, Valerie's work raises the possibility that tumors can be treated by altering the elasticity of the extracellular matrix."

The center, which will be part of the California Institute for Quantitative Biosciences (QB3), will also collaborate with scientists and clinicians from Duke University's Comprehensive Cancer Center Breast Cancer Program and New York University's Breast Cancer and Translational Cancer Research Program.